Dr David J Allen


Associate Professor in Virology
BSc(Hons), PhD, FHEA
On-campus | Monday - Friday

About

Research

Research interests

Publications

C. W. Holmes, S. Rahman, D. J. Allen, S. Bandi, J. W. Tang (2017)Human parechovirus cluster in the UK, 8 May-2 August 2016-sequence analysis, In: Journal of clinical virology9337pp. 37-39 Elsevier
A. Douglas, F. G. Sandmann, D. J. Allen, C. C. Celma, S. Beard, L. Larkin (2021)Impact of COVID-19 on national surveillance of norovirus in England and potential risk of increased disease activity in 2021, In: The Journal of hospital infection112pp. 124-126 Elsevier
Eddie M. Wampande, Peter Waiswa, David J. Allen, Roger Hewson, Simon D. W. Frost, Samuel C. B. Stubbs (2021)Phylogenetic Characterization of Crimean-Congo Hemorrhagic Fever Virus Detected in African Blue Ticks Feeding on Cattle in a Ugandan Abattoir, In: Microorganisms (Basel)9(2)438pp. 1-12 Mdpi

Crimean-Congo hemorrhagic fever virus (CCHFV) is the most geographically widespread of the tick-borne viruses. However, African strains of CCHFV are poorly represented in sequence databases. In addition, almost all sequence data collected to date have been obtained from cases of human disease, while information regarding the circulation of the virus in tick and animal reservoirs is severely lacking. Here, we characterize the complete coding region of a novel CCHFV strain, detected in African blue ticks (Rhipicephalus (Boophilus) decoloratus) feeding on cattle in an abattoir in Kampala, Uganda. These cattle originated from a farm in Mbarara, a major cattle-trading hub for much of Uganda. Phylogenetic analysis indicates that the newly sequenced strain belongs to the African genotype II clade, which predominantly contains the sequences of strains isolated from West Africa in the 1950s, and South Africa in the 1980s. Whilst the viral S (nucleoprotein) and L (RNA polymerase) genome segments shared >90% nucleotide similarity with previously reported genotype II strains, the glycoprotein-coding M segment shared only 80% nucleotide similarity with the next most closely related strains, which were derived from ticks in Western India and Northern China. This genome segment also displayed a large number of non-synonymous mutations previously unreported in the genotype II strains. Characterization of this novel strain adds to our limited understanding of the natural diversity of CCHFV circulating in both ticks and in Africa. Such data can be used to inform the design of vaccines and diagnostics, as well as studies exploring the epidemiology and evolution of the virus for the establishment of future CCHFV control strategies.

Kah Wee Teo, Florence Y. L. Lai, Srini Bandi, David J. Allen, Julian W. Tang (2019)Emergence of Coxsackie A6 hand-foot-and-mouth disease and comparative severity of Coxsackie B vs. echovirus infections, 2014-2016, UK, In: The Journal of infection78(1)75pp. 84-86 Elsevier
Frank G Sandmann, Laura Shallcross, Natalie Adams, David J Allen, Pietro G Coen, Annette Jeanes, Zisis Kozlakidis, Lesley Larkin, Fatima Wurie, Julie V Robotham, Mark Jit, Sarah R Deeny (2018)Estimating the Hospital Burden of Norovirus-Associated Gastroenteritis in England and Its Opportunity Costs for Nonadmitted Patients, In: Clinical infectious diseases67(5)pp. 693-700 Oxford University Press

Since the introduction of rotavirus vaccination in England in July 2013, norovirus has become the second-largest contributor of inpatient gastroenteritis, preventing 57800 patients from being admitted annually. Economic costs amount to £297.7 million, which translates into 6300 quality-adjusted life years.

John P. Harris, Miren Iturriza-Gomara, David J. Allen, Susan Kelly, Sarah J. O’Brien (2019)Norovirus strain types found within the second infectious intestinal diseases (IID2) study an analysis of norovirus circulating in the community, In: BMC infectious diseases19(1)87pp. 87-87 BioMed Central
Mari Morgan, Vicky Watts, David Allen, Daniele Curtis, Amir Kirolos, Neil Macdonald, Ellie Maslen, Deb Morgan, Ayoub Saei, James Sedgwick, Janet Stevenson, Deborah Turbitt, Roberto Vivancos, Catriona Waugh, Chris Williams, Valerie Decraene (2019)Challenges of investigating a large food-borne norovirus outbreak across all branches of a restaurant group in the United Kingdom, October 2016, In: Euro surveillance : bulletin européen sur les maladies transmissibles24(18)1800511pp. 2-11 Eur Centre Dis Prevention & Control

During October and November 2016, over 1,000 customers and staff reported gastroenteritis after eating at all 23 branches of a restaurant group in the United Kingdom. The outbreak coincided with a new menu launch and norovirus was identified as the causative agent. We conducted four retrospective cohort studies; one among all restaurant staff and three in customers at four branches. We investigated the dishes consumed, reviewed recipes, interviewed chefs and inspected restaurants to identify common ingredients and preparation methods for implicated dishes. Investigations were complicated by three public health agencies concurrently conducting multiple analytical studies, the complex menu with many shared constituent ingredients and the high media attention. The likely source was a contaminated batch of a nationally distributed ingredient, but analytical studies were unable to implicate a single ingredient. The most likely vehicle was a new chipotle chilli product imported from outside the European Union, that was used uncooked in the implicated dishes. This outbreak exemplifies the possibility of rapid spread of infectious agents within a restaurant supply chain, following introduction of a contaminated ingredient. It underlines the importance of appropriate risk assessments and control measures being in place, particularly for new ingredients and ready-to-eat foods.

Jake D'Addiego, Sonal Shah, Ayşe Nur Pektaş, Bi̇nnur Köksal Bağci, Murtaza Öz, Sasha Sebastianelli, Nazif Elaldı, David J Allen, Roger Hewson (2024)Development of targeted whole genome sequencing approaches for Crimean-Congo haemorrhagic fever virus (CCHFV), In: Virus research350199464 Elsevier

• A novel probe capture hybridisation method has been developed for CCHFV. • The presented methodology was validated against clinical as well as cell-cultured reference viruses. • The newly developed methodology produced near complete genome coverages at 10x sequencing depths. • Successful recovery of genomes from different CCHFV genetic lineages was achieved. Crimean-Congo haemorrhagic fever (CCHF) is the most prevalent human tick-borne viral disease, with a reported case fatality rate of 30 % or higher. The virus contains a tri-segmented, negative-sense RNA genome consisting of the small (S), medium (M) and large (L) segments encoding respectively the nucleoprotein (NP), the glycoproteins precursor (GPC) and the viral RNA-dependent RNA polymerase (RDRP). CCHFV is one of the most genetically diverse arboviruses, with seven distinct lineages named after the region they were first reported in and based on S segment phylogenetic analysis. Due to the high genetic divergence of the virus, a single targeted tiling PCR strategy to enrich for viral nucleic acids prior to sequencing is difficult to develop, and previously we have developed and validated a tiling PCR enrichment method for the Europe 1 genetic lineage. We have developed a targeted, probe hybridisation capture method and validated its performance on clinical as well as cell-cultured material of CCHFV from different genetic lineages, including Europe 1, Europe 2, Africa 2 and Africa 3. The method produced over 95 % reference coverages with at least 10x sequencing depth. While we were only able to recover a single complete genome sequence from the tested Europe 1 clinical samples with the capture hybridisation protocol, the data provides evidence of its applicability to different CCHFV genetic lineages. CCHFV is an important tick-borne human pathogen with wide geographical distribution. Environmental as well as anthropogenic factors are causing increased CCHFV transmission. Development of strategies to recover CCHFV sequences from genetically diverse lineages of the virus is of paramount importance to monitor the presence of the virus in new areas, and in public health responses for CCHFV molecular surveillance to rapidly detect, diagnose and characterise currently circulating strains.

Kathleen M O'Reilly, David J Allen, Paul Fine, Humayun Asghar (2020)The challenges of informative wastewater sampling for SARS-CoV-2 must be met: lessons from polio eradication, In: The Lancet. Microbe1(5)pp. e189-e190
David J. Allen, John P. Harris (2017)Methods for ascertaining norovirus disease burdens, In: Human vaccines & immunotherapeutics13(11)2630pp. 2630-2636 Taylor & Francis

Norovirus is the commonest cause of gastrointestinal disease worldwide in. Infections with norovirus occur in all age groups, however, the highest incidence is in children aged less than five years. Surveillance of norovirus is complicated because most people do not contact medical services when they are ill. Nevertheless, Public health laboratory surveillance worldwide has demonstrated the dominance of GII.4 viruses in the population. Better epidemiological surveillance and outbreak investigations, coupled with wider implementation of molecular-based laboratory diagnostics are leading to better estimates of the burden of norovirus infections as well as improved outbreak control. Recent advances in cell culture systems for norovirus and current research investigating the distribution of norovirus-associated disease in the population, for whom the disease burden is greatest, understanding host susceptibility factors, and methodologies for ascertaining cases, are important in increasing our understanding of norovirus. The key to surveillance of norovirus is allying the epidemiology with surveillance of virology. With recent advances in laboratory culture systems for norovirus, next generation sequencing technologies, improved diagnostics and measuring phenotypic characteristics of noroviruses, there are new opportunities to advance understanding of this common and important human pathogen that will help design strategies for vaccine and antiviral development, and how these might be best deployed to control norovirus infection.

Alice J. Fraser, Caitlin Greenland-Bews, Daniel Kelly, Christopher T. Williams, Richard Body, Emily R. Adams, Ana Cubas Atienzar, Thomas Edwards, David J. Allen (2023)A high-resolution melt curve toolkit to identify lineage-defining SARS-CoV-2 mutations, In: Scientific reports13(1)3887pp. 3887-3887 Nature Publishing Group UK

The emergence of severe acute respiratory syndrome 2 (SARS-CoV-2) variants of concern (VOCs), with mutations linked to increased transmissibility, vaccine escape and virulence, has necessitated the widespread genomic surveillance of SARS-CoV-2. This has placed a strain on global sequencing capacity, especially in areas lacking the resources for large scale sequencing activities. Here we have developed three separate multiplex high-resolution melting assays to enable the identification of Alpha, Beta, Delta and Omicron VOCs. The assays were evaluated against whole genome sequencing on upper-respiratory swab samples collected during the Alpha, Delta and Omicron [BA.1] waves of the UK pandemic. The sensitivities of the eight individual primer sets were all 100%, and specificity ranged from 94.6 to 100%. The multiplex HRM assays have potential as a tool for high throughput surveillance of SARS-CoV-2 VOCs, particularly in areas with limited genomics facilities.

Christopher Ruis, Sunando Roy, Julianne R Brown, David J Allen, Richard A Goldstein, Judith Breuer (2017)The emerging GII.P16-GII.4 Sydney 2012 norovirus lineage is circulating worldwide, arose by late-2014 and contains polymerase changes that may increase virus transmission, In: PloS one12(6)e0179572pp. e0179572-e0179572

Noroviruses are a leading cause of human gastroenteritis worldwide. The norovirus genotype GII.4 is the most prevalent genotype in the human population and has caused six pandemics since 1995. A novel norovirus lineage containing the GII.P16 polymerase and pandemic GII.4 Sydney 2012 capsid was recently detected in Asia and Germany. We demonstrate that this lineage is also circulating within the UK and USA and has been circulating since October 2014 or earlier. While the lineage does not contain unique substitutions in the capsid, it does contain polymerase substitutions close to positions known to influence polymerase function and virus transmission. These polymerase substitutions are shared with a GII.P16-GII.2 virus that dominated outbreaks in Germany in Winter 2016. We suggest that the substitutions in the polymerase may have resulted in a more transmissible virus and the combination of this polymerase and the pandemic GII.4 capsid may result in a highly transmissible virus. Further surveillance efforts will be required to determine whether the GII.P16-GII.4 Sydney 2012 lineage increases in frequency over the coming months.

Kathleen M O'Reilly, Frank Sandman, David Allen, Christopher I Jarvis, Amy Gimma, Amy Douglas, Lesley Larkin, Kerry Lm Wong, Marc Baguelin, Ralph S Baric, Lisa C Lindesmith, Richard A Goldstein, Judith Breuer, W John Edmunds Predicted Norovirus Resurgence in 2021-2022 Due to the Relaxation of Nonpharmaceutical Interventions Associated with COVID-19 Restrictions in England: A Mathematical Modelling Study, In: medRxiv : the preprint server for health sciences

To reduce the coronavirus disease burden in England, along with many other countries, the Government implemented a package of non-pharmaceutical interventions (NPIs) that have also impacted other transmissible infectious diseases such as norovirus. It is unclear what future norovirus disease incidence is likely to look like upon lifting these restrictions. Here we use a mathematical model of norovirus fitted to community incidence data in England to project forward expected incidence based on contact surveys that have been collected throughout 2020-2021. We report that susceptibility to norovirus infection has likely increased between March 2020 to mid-2021. Depending upon assumptions of future contact patterns incidence of norovirus that is similar to pre-pandemic levels or an increase beyond what has been previously reported is likely to occur once restrictions are lifted. Should adult contact patterns return to 80% of pre-pandemic levels the incidence of norovirus will be similar to previous years. If contact patterns return to pre-pandemic levels there is a potential for the expected annual incidence to be up to 2-fold larger than in a typical year. The age-specific incidence is similar across all ages. Continued national surveillance for endemic diseases such as norovirus will be essential after NPIs are lifted to allow healthcare services to adequately prepare for a potential increase in cases and hospital pressures beyond what is typically experienced.

Claire Guest, Sarah Dewhirst, Steve Lindsay, David Allen, Sophie Aziz, Oliver Baerenbold, John Bradley, Unnati Chabildas, Vanessa Chen-Hussey, Samuel Clifford, Luke Cottis, Jessica Dennehy, Erin Foley, Salvador Gezan, Tim Gibson, Courtenay Greaves, Immo Kleinschmidt, Sébastien Lambert, Anna Last, Steve Morant, Josephine Parker, John Pickett, Billy Quilty, Ann Rooney, Manil Shah, Mark Somerville, Chelci Squires, Martin Walker, James Logan (2022)Using trained dogs and organic semi-conducting sensors to identify asymptomatic and mild SARS-CoV-2 infections: an observational study, In: Journal of travel medicine29(3)taac043 Wiley-Blackwell

Background: A rapid, accurate, non-invasive diagnostic screen is needed to identify people with SARS-CoV-2 infection. We investigated whether organic semi-conducting (OSC) sensors and trained dogs could distinguish between people infected with asymptomatic or mild symptoms, and uninfected individuals, and the impact of screening at ports-of-entry. Methods: Odour samples were collected from adults, and SARS-CoV-2 infection status confirmed using RT-PCR. OSC sensors captured the volatile organic compound (VOC) profile of odour samples. Trained dogs were tested in a double-blind trial to determine their ability to detect differences in VOCs between infected and uninfected

Kathleen M O'Reilly, Frank Sandman, David Allen, Christopher I Jarvis, Amy Gimma, Amy Douglas, Lesley Larkin, Kerry L M Wong, Marc Baguelin, Ralph S Baric, Lisa C Lindesmith, Richard A Goldstein, Judith Breuer, W John Edmunds (2021)Predicted norovirus resurgence in 2021-2022 due to the relaxation of nonpharmaceutical interventions associated with COVID-19 restrictions in England: a mathematical modeling study, In: BMC medicine19(1)299pp. 299-299

To reduce the coronavirus disease burden in England, along with many other countries, the government implemented a package of non-pharmaceutical interventions (NPIs) that have also impacted other transmissible infectious diseases such as norovirus. It is unclear what future norovirus disease incidence is likely to look like upon lifting these restrictions. Here we use a mathematical model of norovirus fitted to community incidence data in England to project forward expected incidence based on contact surveys that have been collected throughout 2020-2021. We report that susceptibility to norovirus infection has likely increased between March 2020 and mid-2021. Depending upon assumptions of future contact patterns incidence of norovirus that is similar to pre-pandemic levels or an increase beyond what has been previously reported is likely to occur once restrictions are lifted. Should adult contact patterns return to 80% of pre-pandemic levels, the incidence of norovirus will be similar to previous years. If contact patterns return to pre-pandemic levels, there is a potential for the expected annual incidence to be up to 2-fold larger than in a typical year. The age-specific incidence is similar across all ages. Continued national surveillance for endemic diseases such as norovirus will be essential after NPIs are lifted to allow healthcare services to adequately prepare for a potential increase in cases and hospital pressures beyond what is typically experienced.

Ira Praharaj, Edward P K Parker, Sidhartha Giri, David J Allen, Sophia Silas, R Revathi, Saravanakumar Puthupalayam Kaliappan, Jacob John, Jasmine Helan Prasad, Beate Kampmann, Miren Iturriza-Gómara, Nicholas C Grassly, Gagandeep Kang (2019)Influence of Nonpolio Enteroviruses and the Bacterial Gut Microbiota on Oral Poliovirus Vaccine Response: A Study from South India, In: The Journal of infectious diseases219(8)1178pp. 1178-1186

Oral poliovirus vaccine (OPV) is less immunogenic in low- or middle-income than in high-income countries. We tested whether bacterial and viral components of the intestinal microbiota are associated with this phenomenon. We assessed the prevalence of enteropathogens using TaqMan array cards 14 days before and at vaccination in 704 Indian infants (aged 6-11 months) receiving monovalent type 3 OPV (CTRI/2014/05/004588). Nonpolio enterovirus (NPEV) serotypes were identified by means of VP1 sequencing. In 120 infants, the prevaccination bacterial microbiota was characterized using 16S ribosomal RNA sequencing. We detected 56 NPEV serotypes on the day of vaccination. Concurrent NPEVs were associated with a reduction in OPV seroconversion, consistent across species (odds ratio [95% confidence interval], 0.57 [.36-.90], 0.61 [.43-.86], and 0.69 [.41-1.16] for species A, B, and C, respectively). Recently acquired enterovirus infections, detected at vaccination but not 14 days earlier, had a greater interfering effect on monovalent type 3 OPV seroresponse than did persistent infections, with enterovirus detected at both time points (seroconversion in 44 of 127 infants [35%] vs 63 of 129 [49%]; P = .02). The abundance of specific bacterial taxa did not differ significantly according to OPV response, although the microbiota was more diverse in nonresponders at the time of vaccination. Enteric viruses have a greater impact on OPV response than the bacterial microbiota, with recent enterovirus infections having a greater inhibitory effect than persistent infections.

K. C. Smith, T. Inns, V. Decraene, A. Fox, D. J. Allen, A. Shah (2017)An outbreak of norovirus GI-6 infection following a wedding in North West England, In: Epidemiology and infection145(6)0950268816003368pp. 1239-1245 Cambridge Univ Press

In August 2015 a gastroenteritis outbreak occurred following a wedding. An outbreak investigation was undertaken and a cohort study was conducted using an online survey. Of 140 guests, 134 received the survey and 113 responded (84 center dot 3% response rate). Seventy respondents met the case definition of vomiting and/or diarrhoea within 72 h of the wedding (61 center dot 9% attack rate). Fifteen exposures were associated with illness; on stratification, all were confounded by the ham hock starter. Multivariable analysis showed a significant association with exposure to ham hock (risk ratio 6 center dot 62, 95% confidence interval 2 center dot 19-20 center dot 03). Eight guests and two catering staff submitted stool samples. All tested positive for norovirus GI-6 infection, including a food handler who had vomiting less than 48 h before the wedding. A single genotype was detected among all samples, suggesting a single source of contamination. The transmission pattern suggested point-source exposure. The most plausible cause of the outbreak was transmission from an infected food handler via contaminated food. This highlights the importance of appropriate exclusions for symptomatic food handlers. Additionally, the food handler's stool sample was submitted 7 days after symptom resolution. The potential for extended viral excretion, and the extremely low infective dose of norovirus, may mean that current exclusion guidelines are not of sufficient duration.

Jade Derrick, Philippa Hollinghurst, Sarah O'Brien, Nicola Elviss, David J. Allen, Miren Iturriza-Gómara (2021)Measuring transfer of human norovirus during sandwich production: Simulating the role of food, food handlers and the environment, In: International journal of food microbiology348109151pp. 109151-109151 Elsevier B.V

Foodborne outbreaks associated with transmission of norovirus are increasingly becoming a public health concern. Foods can be contaminated with faecal material at the point of production or during food preparation, in both the home and in commercial premises. Transmission of norovirus occurs through the faecal-oral route, either via person-to-person contact or through faecal-contamination of food, water, or environmental surfaces. Understanding the role and pathways of norovirus transmission – either via food handlers' hands, contaminated foods or the environment – remains a key public health priority to reduce the burden of norovirus-associated gastroenteritis. However the proportion of norovirus that is typically transferred remains unknown. Understanding this is necessary to estimate the risk of infection and the burden of gastroenteritis caused by norovirus. In this paper we present a novel method of capture, concentration and molecular detection of norovirus from a wider range of complex food matrices than those demonstrated in existing published methods. We demonstrate that this method can be used as a tool to detect and quantify norovirus from naturally contaminated food, and for monitoring norovirus transfer between food handlers' gloved hands, food or the environment. We measure the effect of introducing contamination at different food production process stages, to the final food product, to determine whether this could cause infection and disease. Between 5.9 and 6.3 Log10 cDNA copies/μl of norovirus GII were inoculated onto food handlers' gloved hands, food or the environment and 1.1–7.4% of norovirus contamination was recovered from all samples tested. When interpreted quantitatively, this percentage equates to levels predicted to be sufficient to cause infection and disease through consumption of the final food product, demonstrating a public health risk. Overall detection and quantification of norovirus from foods, food handlers' gloved hands and the environment, when suspected to be implicated in foodborne transmissions, is paramount for appropriate outbreak investigation. •Detection of norovirus from 13 ready-to-eat food categories; a wider range of food samples than previously published.•Norovirus RNA detection and quantification from hands, food and the environment can support public health responses.•Detection and quantification of norovirus RNA in the final food product can be used to assess risk to the consumer.

K. M. O'Reilly, N. C. Grassly, D. J. Allen, M. Bannister-Tyrrell, A. Cameron, A. I. Carrion Martin, M. Ramsay, R. Pebody, M. Zambon (2020)Surveillance optimisation to detect poliovirus in the pre-eradication era: a modelling study of England and Wales, In: Epidemiology and infection1480950268820001004pp. e157-e157 Cambridge Univ Press

Surveillance for acute flaccid paralysis (AFP) cases are essential for polio eradication. However, as most poliovirus infections are asymptomatic and some regions of the world are inaccessible, additional surveillance tools require development. Within England and Wales, we demonstrate how inclusion of environmental sampling (ENV) improves the sensitivity of detecting both wild and vaccine-derived polioviruses (VDPVs) when compared to current surveillance. Statistical modelling was used to estimate the spatial risk of wild and VDPV importation and circulation in England and Wales. We estimate the sensitivity of each surveillance mode to detect poliovirus and the probability of being free from poliovirus, defined as being below a pre-specified prevalence of infection. Poliovirus risk was higher within local authorities in Manchester, Birmingham, Bradford and London. The sensitivity of detecting wild poliovirus within a given month using AFP and enterovirus surveillance was estimated to be 0.096 (95% CI 0.055-0.134). Inclusion of ENV in the three highest risk local authorities and a site in London increased surveillance sensitivity to 0.192 (95% CI 0.191-0.193). The sensitivity of ENV strategies can be compared using the framework by varying sites and the frequency of sampling. The probability of being free from poliovirus slowly increased from the date of the last case in 1993. ENV within areas thought to have the highest risk improves detection of poliovirus, and has the potential to improve confidence in the polio-free status of England and Wales and detect VDPVs.

Manasi Majumdar, Dimitra Klapsa, Thomas Wilton, Joyce Akello, Catherine Anscombe, David Allen, Edward T. Mee, Philip D. Minor, Javier Martin (2018)Isolation of Vaccine-Like Poliovirus Strains in Sewage Samples From the United Kingdom, In: The Journal of infectious diseases217(8)1222pp. 1222-1230 Oxford Univ Press

Background. Environmental surveillance (ES) is a sensitive method for detecting human enterovirus (HIEV) circulation, and it is used worldwide to support global polio eradication. We describe a novel ES approach using next-generation sequencing (NGS) to identify HEVs in sewage samples collected in London, United Kingdom, from June 2016 to May 2017. Methods. Two different methods were used to process raw sewage specimens: a 2-phase aqueous separation system and size exclusion by filtration and centrifugation. HEVs were isolated using cell cultures and analyzed using NGS. Results. Type 1 and 3 vaccine-like poliovirus (PV) strains were detected in samples collected from September 2016 through January 2017. NGS analysis allowed us to rapidly obtain whole-genome sequences of PV and non-PV HEV strains. As many as 6 virus strains from different HEV serotypes were identified in a single cell culture flask. PV isolates contained only a small number of mutations from vaccine strains commonly seen in early isolates from vaccinees. Conclusions. Our ES setup has high sensitivity for polio and non-PV HEV detection, generating nearly whole-genome sequence information. Such ES systems provide critical information to assist the polio eradication endgame and contribute to the improvement of our understanding of HEV circulation patterns in humans.

Seilesh Kadambari, Serena Braccio, Sonia Ribeiro, David J Allen, Richard Pebody, David Brown, Robert Cunney, Mike Sharland, Shamez Ladhani (2019)Enterovirus and parechovirus meningitis in infants younger than 90 days old in the UK and Republic of Ireland: a British Paediatric Surveillance Unit study, In: Archives of disease in childhood104(6)pp. 552-557

ObjectivesThis study aimed to prospectively collect detailed clinical information for all enterovirus (EV) and human parechovirus (HPeV) meningitis cases in infants aged

Heli Harvala, Eeva Broberg, Kimberley Benschop, Natasa Berginc, Shamez Ladhani, Petri Susi, Claus Christiansen, James McKenna, David Allen, Phoebe Makiello, Georgina McAllister, Mirabelli Carmen, Katherina Zakikhany, Robert Dyrdak, Xiaohui Nielsen, Tina Madsen, Joel Paul, Catherine Moore, Karin von Eije, Antonio Piralla, Mieke Carlier, Laura Vanoverschelde, Randy Poelman, Andrés Anton, F Xavier López-Labrador, Laura Pellegrinelli, Kathrin Keeren, Melanie Maier, Hayley Cassidy, Stavros Derdas, Carita Savolainen-Kopra, Sabine Diedrich, Svein Nordbø, Javier Buesa, Jean-Luc Bailly, Fausto Baldanti, Andrew MacAdam, Audrey Mirand, Susanne Dudman, Isabelle Schuffenecker, Seilesh Kadambari, Johan Neyts, Michael J Griffiths, Jan Richter, Cristina Margaretto, Sheila Govind, Ursula Morley, Ortwin Adams, Sidsel Krokstad, Jonathan Dean, Margarita Pons-Salort, Birgit Prochazka, Maria Cabrerizo, Manasi Majumdar, Gaia Nebbia, Maryse Wiewel, Simon Cottrell, Peter Coyle, Javier Martin, Catrin Moore, Sofie Midgley, Peter Horby, Katja Wolthers, Peter Simmonds, Hubert Niesters, Thea K Fischer (2018)Recommendations for enterovirus diagnostics and characterisation within and beyond Europe, In: Journal of clinical virology101pp. 11-17

Enteroviruses (EV) can cause severe neurological and respiratory infections, and occasionally lead to devastating outbreaks as previously demonstrated with EV-A71 and EV-D68 in Europe. However, these infections are still often underdiagnosed and EV typing data is not currently collected at European level. In order to improve EV diagnostics, collate data on severe EV infections and monitor the circulation of EV types, we have established European non-polio enterovirus network (ENPEN). First task of this cross-border network has been to ensure prompt and adequate diagnosis of these infections in Europe, and hence we present recommendations for non-polio EV detection and typing based on the consensus view of this multidisciplinary team including experts from over 20 European countries. We recommend that respiratory and stool samples in addition to cerebrospinal fluid (CSF) and blood samples are submitted for EV testing from patients with suspected neurological infections. This is vital since viruses like EV-D68 are rarely detectable in CSF or stool samples. Furthermore, reverse transcriptase PCR (RT-PCR) targeting the 5'noncoding regions (5'NCR) should be used for diagnosis of EVs due to their sensitivity, specificity and short turnaround time. Sequencing of the VP1 capsid protein gene is recommended for EV typing; EV typing cannot be based on the 5'NCR sequences due to frequent recombination events and should not rely on virus isolation. Effective and standardized laboratory diagnostics and characterisation of circulating virus strains are the first step towards effective and continuous surveillance activities, which in turn will be used to provide better estimation on EV disease burden.

Daniel Hungerford, David J Allen, Sameena Nawaz, Sarah Collins, Shamez Ladhani, Roberto Vivancos, Miren Iturriza-Gómara (2019)Impact of rotavirus vaccination on rotavirus genotype distribution and diversity in England, September 2006 to August 2016, In: Euro surveillance : bulletin européen sur les maladies transmissibles24(6)1700774pp. 38-48

IntroductionRotavirus vaccination with the live-attenuated monovalent (a G1P[8] human rotavirus strain) two-dose Rotarix vaccine was introduced in England in July 2013. Since then, there have been significant reductions in rotavirus gastroenteritis incidence.AimWe assessed the vaccine's impact on rotavirus genotype distribution and diversity 3 years post-vaccine introduction.MethodsEpidemiological and microbiological data on genotyped rotavirus-positive samples between September 2006 and August 2016 were supplied by EuroRotaNet and Public Health England. Multinomial multivariable logistic regression adjusting for year, season and age was used to quantify changes in genotype prevalence in the vaccine period. Genotype diversity was measured using the Shannon's index (H') and Simpson's index of diversity (D).ResultsWe analysed genotypes from 8,044 faecal samples. In the pre-vaccine era, G1P[8] was most prevalent, ranging from 39% (411/1,057) to 74% (527/709) per year. In the vaccine era, G1P[8] prevalence declined each season (35%, 231/654; 12%, 154/1,257; 5%, 34/726) and genotype diversity increased significantly in 6-59 months old children (H' p 

Thomas Inns, Anna Pulawska-Czub, John P Harris, Roberto Vivancos, Jonathan M Read, Nicholas J Beeching, David J Allen, Miren Iturriza-Gomara, Sarah J O’Brien (2017)Prospective cohort study to investigate the burden and transmission of acute gastroenteritis in care homes: a study protocol, In: BMJ open7(11)e018867pp. e018867-e018867

IntroductionNoroviruses are the leading cause of acute gastroenteritis in all age groups, but illness is more severe and causes excess mortality in the elderly, particularly those in long-term care. The total burden of norovirus disease in the elderly in the UK is poorly defined; no current surveillance programmes systematically or accurately quantify norovirus infection in those living in care homes. The aim of this study is to evaluate an enhanced surveillance system for acute gastroenteritis among the elderly in care homes.Methods and analysisWe will conduct this prospective cohort study in care homes in North West England; residents and staff at study care homes will be asked to participate. We will prospectively enrol a cohort of participants in an enhanced surveillance system to capture the incidence of acute gastroenteritis and use multiplex PCR to detect pathogens. We will sample symptomatic and non-symptomatic participants to understand characteristics of norovirus disease and susceptibility to infection. We will generate novel data on transmission dynamics by collecting data on the pattern of interactions within care homes using electronic proximity sensors. Comparisons of outbreak and non-outbreak periods will be used to quantify the impact of norovirus outbreaks on care homes.Ethics and disseminationThe study has been approved by the North West–Greater Manchester South NHS Research Ethics Committee (REC Reference: 16/NW/0541). Study outputs will be disseminated through scientific conferences and peer-reviewed publications. This study will provide detailed insight on the burden and aetiology of acute gastroenteritis in care homes, in addition to generating novel data on transmission dynamics and risks. The study will identify areas for improving infection control practice and allow more accurate modelling of the introduction of interventions such as vaccination.

Laura Ferreras Antolín, Seilesh Kadambari, Serena Braccio, Julian Wei-Tze Tang, Jacqueline Xerry, David James Allen, Shamez N Ladhani (2018)Increased detection of human parechovirus infection in infants in England during 2016: epidemiology and clinical characteristics, In: Archives of disease in childhood103(11)pp. 1061-1066

BackgroundHuman parechovirus (HPeV), like enteroviruses, usually causes mild self-limiting respiratory and gastrointestinal symptoms. In infants, HPeV can occasionally cause serious illnesses, including sepsis-like syndrome and encephalitis. In summer 2016, Public Health England (PHE) received increasing reports of severe HPeV infections nationally. We, therefore, reviewed all infants with confirmed HPeV across England during 2016.MethodsHPeV cases in infants aged

Jemma L. Walker, Nick J. Andrews, Christina J. Atchison, Sarah Collins, David J. Allen, Mary E. Ramsay, Shamez N. Ladhani, Sara L. Thomas (2019)Effectiveness of oral rotavirus vaccination in England against rotavirus-confirmed and all-cause acute gastroenteritis, In: Vaccine: X1100005pp. 100005-100005 Elsevier

• Rotarix® had very good vaccine effectiveness (VE) in UK public health use. • Two-dose VE against confirmed infection in young children was 77% (95%CI:66–85%) • The vaccine programme was exceptionally successful (>90% vaccine uptake, high VE) • Thus, it is highly likely that most acute gastroenteritis (AGE) was no longer due to rotavirus. • This explains the lack of demonstrable VE against all-cause AGE.

A. I. CARRION Martin, R. G. Pebody, K. Danis, J. Ellis, S. Niazi, S. DE LUSIGNAN, K. E. Brown, M. Zambon, D. J. Allen (2017)The emergence of enterovirus D68 in England in autumn 2014 and the necessity for reinforcing enterovirus respiratory screening, In: Epidemiology and infection145(9)1855:1864pp. 1855-1864 Cambridge University Press

In autumn 2014, enterovirus D68 (EV-D68) cases presenting with severe respiratory or neurological disease were described in countries worldwide. To describe the epidemiology and virological characteristics of EV-D68 in England, we collected clinical information on laboratory-confirmed EV-D68 cases detected in secondary care (hospitals), between September 2014 and January 2015. In primary care (general practitioners), respiratory swabs collected (September 2013–January 2015) from patients presenting with influenza-like illness were tested for EV-D68. In secondary care 55 EV-D68 cases were detected. Among those, 45 cases had clinical information available and 89% (40/45) presented with severe respiratory symptoms. Detection of EV-D68 among patients in primary care increased from 0.4% (4/1074; 95% CI 0.1–1.0) (September 2013–January 2014) to 0.8% (11/1359; 95% CI 0.4–1.5) (September 2014–January 2015). Characterization of EV-D68 strains circulating in England since 2012 and up to winter 2014/2015 indicated that those strains were genetically similar to those detected in 2014 in USA. We recommend reinforcing enterovirus surveillance through screening respiratory samples of suspected cases.

Lisa C Lindesmith, Florencia A T Boshier, Paul D Brewer-Jensen, Sunando Roy, Veronica Costantini, Michael L Mallory, Mark Zweigart, Samantha R May, Helen Conrad, Kathleen M O'Reilly, Daniel Kelly, Cristina C Celma, Stuart Beard, Rachel Williams, Helena J Tutill, Sylvia Becker Dreps, Filemón Bucardo, David J Allen, Jan Vinjé, Richard A Goldstein, Judith Breuer, Ralph S Baric (2022)Immune Imprinting Drives Human Norovirus Potential for Global Spread, In: mBio13(5)pp. e0186122-e0186122

Understanding the complex interactions between virus and host that drive new strain evolution is key to predicting the emergence potential of variants and informing vaccine development. Under our hypothesis, future dominant human norovirus GII.4 variants with critical antigenic properties that allow them to spread are currently circulating undetected, having diverged years earlier. Through large-scale sequencing of GII.4 surveillance samples, we identified two variants with extensive divergence within domains that mediate neutralizing antibody binding. Subsequent serological characterization of these strains using temporally resolved adult and child sera suggests that neither candidate could spread globally in adults with multiple GII.4 exposures, yet young children with minimal GII.4 exposure appear susceptible. Antigenic cartography of surveillance and outbreak sera indicates that continued population exposure to GII.4 Sydney 2012 and antigenically related variants over a 6-year period resulted in a broadening of immunity to heterogeneous GII.4 variants, including those identified here. We show that the strongest antibody responses in adults exposed to GII.4 Sydney 2012 are directed to previously circulating GII.4 viruses. Our data suggest that the broadening of antibody responses compromises establishment of strong GII.4 Sydney 2012 immunity, thereby allowing the continued persistence of GII.4 Sydney 2012 and modulating the cycle of norovirus GII.4 variant replacement. Our results indicate a cycle of norovirus GII.4 variant replacement dependent upon population immunity. Young children are susceptible to divergent variants; therefore, emergence of these strains worldwide is driven proximally by changes in adult serological immunity and distally by viral evolution that confers fitness in the context of immunity. In our model, preepidemic human norovirus variants harbor genetic diversification that translates into novel antigenic features without compromising viral fitness. Through surveillance, we identified two viruses fitting this profile, forming long branches on a phylogenetic tree. Neither evades current adult immunity, yet young children are likely susceptible. By comparing serological responses, we demonstrate that population immunity varies by age/exposure, impacting predicted susceptibility to variants. Repeat exposure to antigenically similar variants broadens antibody responses, providing immunological coverage of diverse variants but compromising response to the infecting variant, allowing continued circulation. These data indicate norovirus GII.4 variant replacement is driven distally by virus evolution and proximally by immunity in adults.

Janko van Beek, Miranda de Graaf, Haider Al-Hello, David Allen, Katia Ambert-Balay, Nadine Botteldoorn, Mia Brytting, Javier Buesa, Maria Cabrerizo, Martin Chan, Fiona Cloak, Ilaria Di Bartolo, Susana Guix, Joanne Hewitt, Nobuhiro Iritani, Miao Jin, Reimar Johne, Ingeborg Lederer, Janet Mans, Vito Martella, Leena Maunula, Georgina Mcallister, Sandra Niendorf, Hubert Niesters, Alexander Podkolzin, Mateja Poljsak-Prijatelj, Lasse Dam Rasmussen, Gábor Reuter, Gráinne Tuite, Annelies Kroneman, Harry Vennema, Marion Koopmans (2018)Molecular surveillance of norovirus, 2005–16 : an epidemiological analysis of data collected from the NoroNet network, In: The Lancet infectious diseases18(5)545pp. 545-553 New York, NY : Elsevier Science ; The Lancet Pub. Group, 2001

BACKGROUND: The development of a vaccine for norovirus requires a detailed understanding of global genetic diversity of noroviruses. We analysed their epidemiology and diversity using surveillance data from the NoroNet network.METHODS: We included genetic sequences of norovirus specimens obtained from outbreak investigations and sporadic gastroenteritis cases between 2005 and 2016 in Europe, Asia, Oceania, and Africa. We genotyped norovirus sequences and analysed sequences that overlapped at open reading frame (ORF) 1 and ORF2. Additionally, we assessed the sampling date and country of origin of the first reported sequence to assess when and where novel drift variants originated.FINDINGS: We analysed 16 635 norovirus sequences submitted between Jan 1, 2005, to Nov 17, 2016, of which 1372 (8·2%) sequences belonged to genotype GI, 15 256 (91·7%) to GII, and seven (

Sally Black, Carina Bradley, Florence Y Lai, Savitha Shenoy, Srini Bandi, David J Allen, Julian W Tang (2019)Comparing the Clinical Severity of Disease Caused by Enteroviruses and Human Parechoviruses in Neonates and Infants, In: The Pediatric infectious disease journal38(2)pp. e36-e38

Comparison of children hospitalized with enterovirus or human parechovirus (HPeV) detected in their cerebrospinal fluid revealed that HPeV infections presented with more persistent fever, irritability and feeding problems, more frequent leukopenia and lymphopenia and higher admission rates to high dependency or intensive care units. Few HPeV cases were followed up, further studies on long-term outcomes are needed.

Lisa C. Lindesmith, Paul D. Brewer-Jensen, Helen Conrad, Kathleen M. O’Reilly, Michael L. Mallory, Daniel Kelly, Rachel Williams, W. John Edmunds, David J. Allen, Judith Breuer, Ralph S. Baric (2023)Emergent variant modeling of the serological repertoire to norovirus in young children, In: Cell reports. Medicine4(3)100954pp. 100954-100954 Elsevier

Human norovirus is the leading cause of acute gastroenteritis. Young children and the elderly bear the greatest burden of disease, representing more than 200,000 deaths annually. Infection prevalence peaks at younger than 2 years and is driven by novel GII.4 variants that emerge and spread globally. Using a surrogate neutralization assay, we characterize the evolution of the serological neutralizing antibody (nAb) landscape in young children as they transition between sequential GII.4 pandemic variants. Following upsurge of the replacement variant, antigenic cartography illustrates remodeling of the nAb landscape to the new variant accompanied by improved nAb titer. However, nAb relative avidity remains focused on the preceding variant. These data support immune imprinting as a mechanism of immune evasion and GII.4 virus persistence across a population. Understanding the complexities of immunity to rapidly evolving and co-circulating viral variants, like those of norovirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), and dengue viruses, will fundamentally inform vaccine design for emerging pathogens. • Sera from young children block binding of antigenically diverse GII.4 noroviruses • GII.4 variant replacement shapes population serological antibody titer over time • High-avidity antibody remains focused on previous, antigenically related GII.4 variants • Immune imprinting molds GII.4 antibody responses and virus emergence potential Norovirus GII.4 variants are a leading cause of gastroenteritis in children. Lindesmith et al. demonstrate that an emergent variant remodels antibody titer, while high-avidity antibody remains focused on the preceding related variant. These data support immune imprinting as a mechanism of GII.4 immune evasion and virus persistence.

Christina J Atchison, Julia Stowe, Nick Andrews, Sarah Collins, David J Allen, Sameena Nawaz, David Brown, Mary E Ramsay, Shamez N Ladhani (2016)Rapid Declines in Age Group-Specific Rotavirus Infection and Acute Gastroenteritis Among Vaccinated and Unvaccinated Individuals Within 1 Year of Rotavirus Vaccine Introduction in England and Wales, In: The Journal of infectious diseases213(2)pp. 243-249

The oral infant rotavirus vaccine, Rotarix, was introduced in England and Wales in July 2013. We estimated the impact on laboratory-confirmed rotavirus infections and hospitalizations for all-cause acute gastroenteritis (AGE) during the first year after introduction. We extracted data on laboratory-confirmed rotavirus infections (July 2000 through June 2015) and all-cause AGE-associated hospitalizations (July 2007 through June 2014) for all age groups using national databases (LabBase2 and HES). We determined the ratio of the rate during the 2013-2014 rotavirus season to the rate during the prevaccination era. In infants, there was a 77% decline (rate ratio [RR], 0.23; 95% confidence interval [CI], .16-.32) in laboratory-confirmed rotavirus infections and a 26% decline (RR, 0.74; 95% CI, .65-.84) in all-cause AGE-associated hospitalizations in 2013-2014, compared with the prevaccination era. Large reductions were also observed in older children, adults, and older adults. We estimated that 10 884 laboratory-confirmed infections and 50 427 all-cause AGE-associated hospital admissions were averted in 2013-2014. Similar reductions have been observed for laboratory-confirmed rotavirus infections during the 2014-2015 season. The rapid declines in rotavirus infection and AGE in vaccinated and unvaccinated age groups within 1 year of introducing an infant rotavirus vaccination program are far greater than expected and than previously reported by other countries.

D Hungerforda, J Readc, RPD Cooked, R Vivancosb, M Iturriza-Gomaraa, D Allene, N Frencha, N Cunliffea, David James Allen (2016)Early impact of rotavirus vaccination in a large paediatric hospital in the UK, In: The Journal of hospital infection93(2)117pp. 117-120

The impact of routine rotavirus vaccination on community-acquired (CA) and healthcare-associated (HA) rotavirus gastroenteritis (RVGE) at a large paediatric hospital, UK, was investigated over a 13-year period. A total of 1644 hospitalized children aged 0-15 years tested positive for rotavirus between July 2002 and June 2015. Interrupted time-series analysis demonstrated that, post vaccine introduction (July 2013 to June 2015), CA- and HA-RVGE hospitalizations were 83% [95% confidence interval (CI): 72-90%) and 83% (95% CI: 66-92%] lower than expected, respectively. Rotavirus vaccination has rapidly reduced the hospital rotavirus disease burden among both CA- and HA-RVGE cases.

Daniel Hungerford, Roberto Vivancos, David James Allen (2016)In-season and out-of-season variation of rotavirus genotype distribution and age of infection across 12 European countries before the introduction of routine vaccination, 2007/08 to 2012/13, In: Euro surveillance : bulletin européen sur les maladies transmissibles21(2)pp. 18-29

The EuroRotaNet surveillance network has conducted rotavirus genotype surveillance since 2007 in 16 European countries. Using epidemiological and microbiological data from 39,786 genotyped rotavirus-positive specimens collected between September 2007 and August 2013, we assessed genotype distribution and age distribution of rotavirus gastroenteritis (RVGE) cases in and out of peak season in 12 countries which were yet to implement routine rotavirus vaccination. In multinomial multivariate logistic regression, adjusting for year, country and age, the odds of infection caused by genotype-constellation 2 DS-1-like stains (adjusted multinomial odds ratio (aM-OR) = 1.25; 95% confidence interval (CI): 1.13–1.37; p 

Christopher W Holmes, Sharon S F Koo, Husam Osman, Steven Wilson, Jacqueline Xerry, Chris I Gallimore, David J Allen, Julian W Tang (2016)Predominance of enterovirus B and echovirus 30 as cause of viral meningitis in a UK population, In: Journal of clinical virology81pp. 90-93

Enteroviruses are the most common cause of aseptic or lymphocytic meningitis, particularly in children. With reports of unusually severe neurological disease in some patients infected with enterovirus D68 in North America, and a recent increase in the number of paediatric enterovirus meningitis cases presenting in this UK Midlands population, a retrospective regional surveillance study was performed. Cerebrospinal fluid (CSF) samples received were tested using the polymerase chain reaction (PCR) for HSV-1/2, VZV, enteroviruses and parechoviruses. Enterovirus PCR positive CSF samples were sent for further serotyping. A phylogenetic tree was constructed of the echovirus 30 VP1 sequences, where sufficient sample remained for sequencing. The number of enterovirus positive CSFs from each year were: 21 (2008), 7 (2011), 53 (2012), 58 (2013) and 31 (2014). Overall, 163 of the 170 serotyped enteroviruses belonged to the species B (echovirus 5, 6, 7, 9, 11, 13, 16, 17, 18, 21, 25, 30; coxsackie B1, B2, B3, B4, B5, A9), with only 7 belonging to species A (coxsackie A2, A6, A16 and enterovirus 71). Echovirus 30 was the predominant serotype overall, identified in 43 (25.3%) of samples, with a significantly higher proportion in the adult age group (37.3%) compared to the infant age group (12.3%). Phylogenetic analysis showed that these UK Midlands echovirus 30 VP1 sequences clustered most closely with those from Europe and China. This study showed a continued predominance of echovirus 30 as a cause of viral meningitis, particularly in adults, though more surveillance is needed.

David J Allen, Natalie L Adams, Farah Aladin, John P Harris, David W G Brown (2014)Emergence of the GII-4 Norovirus Sydney2012 strain in England, winter 2012-2013, In: PloS one9(2)e88978pp. e88978-e88978

Norovirus is the commonest cause of acute gastrointestinal disease and is the main aetiological agent of outbreaks of gastroenteritis, particularly in semi-closed environments. Norovirus infections in England typically peak between December and March each year. The most commonly detected norovirus strains belong to the genetically diverse genogroup-II genotype-4 (GII-4) genocluster and in the previous two norovirus winter seasons the majority of GII-4 strains in circulation worldwide have been genetically similar to the GII-4 strain New Orleans 1805/2009/USA. At the beginning of the 2012/13 season a genetically distinct GII-4 strain (Sydney 2012/NSW0514/2012/AU) was described which emerged worldwide during the winter of 2012/13. Here we describe the emergence of norovirus strains genetically related to Sydney2012 in England during the 2012/13 season to replace NewOrleans2009 strains as the most commonly detected variant of GII-4 norovirus in England. Furthermore, we demonstrate that whilst the emergence of Sydney2012 coincided with an early peak in the number of norovirus outbreaks, there was not an overall increase in norovirus activity compared to the previous season. Finally, we show that the Sydney2012 strain is associated with distinct genetic changes compared to the NewOrleans2009 strain, and these changes may have contributed to the emergence of the Sydney2012 strain.

Katherina Zakikhany, David J. Allen, David Brown, Miren Iturriza-Gomara (2012)Molecular Evolution of GII-4 Norovirus Strains, In: PloS one7(7)41625pp. e41625-e41625 Public Library Science

Background: Human Noroviruses (NoV) are the major cause of acute nonbacterial gastroenteritis and the leading cause of outbreaks of gastroenteritis worldwide. Genotype II-4 (GII-4) NoV has been shown to spread rapidly and is the most commonly detected strain worldwide, particularly in association with outbreaks. Previously, we have shown that circulating GII-4 NoV strains exist as populations of selectively neutral variants, and that the emergence of epidemic GII-4 NoV strains correlated with mutations in at least two key sites (Sites A and B) within the P2 domain of the surface exposed major capsid protein (VP1). Methodology: We developed a rapid pyrosequencing method for screening of the two Sites A and B and a homology based modelling system was used to predict the effects of amino acid substitutions at these sites on the antigenic properties of the virus (defined as surface motif types). Principle Finding/Conclusion: Here, we describe the characterisation of amino acid diversity at Sites A and B for 1062 GII-4 NoV strains from clinical specimen associated with outbreak of gastroenteritis (2000-2011) and 250 GII-4 NoV sequences from Genbank. Our data identified a high diversity of different Site A and B site combinations at amino acid level and amino acid diversity was higher at Site B than Site A. Site A motifs could be grouped into 3 clusters based on similar surface motif types. We predict that Site A is a major epitope on the virus surface, responsible for defining the antigenic profile, and a more subtle role for Site B, maintaining minor antigenic variation within the virus population.

Sameena Nawaz, David J. Allen, Farah Aladin, Christopher Gallimore, Miren Iturriza-Gómara (2012)Human Bocaviruses Are Not Significantly Associated with Gastroenteritis: Results of Retesting Archive DNA from a Case Control Study in the UK, In: PloS one7(7)e41346pp. e41346-e41346 Public Library of Science

Gastroenteritis is a common illness causing considerable morbidity and mortality worldwide. Despite improvements in detection methods, a significant diagnostic gap still remains. Human bocavirus (HBoV)s, which are associated with respiratory infections, have also frequently been detected in stool samples in cases of gastroenteritis, and a tentative association between HBoVs, and in particular type-2 HBoVs, and gastroenteritis has previously been made. The aim of this study was to determine the role of HBoVs in gastroenteritis, using archived DNA samples from the case-control Infectious Intestinal Disease Study (IID). DNA extracted from stool samples from 2,256 cases and 2,124 controls were tested for the presence of HBoV DNA. All samples were screened in a real time PCR pan-HBoV assay, and positive samples were then tested in genotype 1 to 3-specific assays. HBoV was detected in 7.4% but no significantly different prevalence was observed between cases and controls. In the genotype-specific assays 106 of the 324 HBoV-positive samples were genotyped, with HBoV-1 predominantly found in controls whilst HBoV-2 was more frequently associated with cases of gastroenteritis (p

D. J. Allen, M. Iturriza-Gomara, D. W. G. Brown (2013)Advances in understanding of norovirus as a food- and waterborne pathogen and progress with vaccine development, In: N Cook (eds.), Viruses in Food and Water - Risks, Surveillance and Controlpp. 319-348 Woodhead Publ Ltd

Noroviruses are the commonest cause of infectious intestinal disease, and are frequently associated with outbreaks of gastroenteritis, mainly in healthcare-associated settings, but also in outbreaks associated with contaminated food and/or water. The contamination of foods can occur during production, preparation, and/or service, or, more rarely by contamination of water supply. Contamination of water supply with norovirus is rare, and usually occurs as a consequence of leakage of sewage or as a result of leaching after heavy rainfall. Outbreaks of norovirus gastroenteritis associated with contaminated food and water can have high impact as a large number of individuals can become affected quickly over a large geographical area, with a high number of secondary cases. However, adequate capture of both epidemiological and laboratory data of norovirus outbreaks remains a major challenge, as many outbreaks fail to be identified and/ or followed up and so the incidence of norovirus-associated foodborne outbreaks is not well defined. Measures for preventing norovirus contamination are centred on good hand hygiene and environmental cleaning practices in healthcare settings, food establishments and on board cruise ships. Several guidelines for responding to outbreaks in food preparation premises are available, and there is a wide range of generic legislation for food processing and handling. There is currently no licenced vaccine or antiviral drug for prophylaxis or treatment of norovirus. However, the first trial demonstrating homologous protection against illness and infection using a norovirus VLP (virus-like particle) was reported recently. Whilst promising, the vaccine is monovalent and the evidence suggests that there is little cross-protection between norovirus strains, a multivalent vaccine is likely to be the only viable option for future vaccine development.

Noelia Carmona-Vicente, David J. Allen, Jesus Rodriguez-Diaz, Miren Iturriza-Gomara, Javier Buesa (2016)Antibodies against Lewis antigens inhibit the binding of human norovirus GII.4 virus-like particles to saliva but not to intestinal Caco-2 cells, In: Virology journal13(1)82pp. 82-82 Springer Nature

Background: Human noroviruses (NoVs) are the main cause of gastroenteritis worldwide. The most commonly detected NoV strains belong to the genetically diverse GII.4 genotype, with new pandemic variants emerging periodically. Despite extensive efforts, NoV investigation has been hampered by the lack of an effective in vitro cell culture system. However, NoV-derived recombinant virus-like particles (VLPs) resembling empty capsids are good surrogates for analysing NoV antigenicity and virus-ligand interactions. NoV VLPs have been reported to bind to histo-blood group antigens (HBGAs). We have analysed the ability of NoV VLPs derived from GI. 1 genotype and from three GII.4 genotype variants, GII.4-1999, GII.4-2004 and GII.4-2006b, to bind to porcine gastric mucin (PGM), human saliva and differentiated human intestinal Caco-2 cells (D-Caco-2 cells). Results: Distinct patterns of saliva binding with the NoV GII.4 variant VLPs were observed, although they bound to D-Caco-2 cells independently of the expression of HBGAs. Monoclonal antibodies against Lewis antigens were able to block the binding of NoV VLPs to saliva, but not to D-Caco-2 cells. Blocking HBGAs on the surface of D-Caco-2 cells with specific monoclonal antibodies did not affect NoV VLP binding to cellular membranes. Co-localisation of Lewis y (Le(y)) and H-type 2 antigens with NoV VLPs was not observed by immunofluorescence assays. Conclusion: Although the binding of NoV VLPs of GII.4 genotype variants to human saliva samples occur with distinct HBGA binding patterns and can be blocked by antibodies against Lewis antigens, their attachment to D-Caco-2 cells can be mediated by other receptors, which still need further investigation.

Jacqueline Xerry, Chris I. Gallimore, Miren Iturriza-Gomara, David J. Allen, Jim J. Gray (2008)Transmission events within outbreaks of gastroenteritis determined through analysis of nucleotide sequences of the P2 domain of genogroup II noroviruses, In: Journal of clinical microbiology46(3)pp. 947-953 Amer Soc Microbiology

Tracking the spread of noroviruses during outbreaks of gastroenteritis is hampered by the lack of sequence diversity in those regions of the genome chosen for virus detection and characterization. Sequence analysis of regions of the genes encoding the RNA-dependent RNA polymerase and the S domain of the capsid does not provide sufficient discrimination between genotypically related strains of different outbreaks. However, analysis of sequences derived from the region encoding the P2 domain showed 100% similarity among strains from the same outbreak and

David J. Allen, Rob Noad, Dhan Samuel, Jim J. Gray, Polly Roy, Miren Iturriza-Gomara (2009)Characterisation of a GII-4 norovirus variant-specific surface-exposed site involved in antibody binding, In: Virology journal6(1)150pp. 150-150 Springer Nature

Background: The human noroviruses are a highly diverse group of viruses with a single-stranded RNA genome encoding a single major structural protein (VP1), which has a hypervariable domain (P2 domain) as the most exposed part of the virion. The noroviruses are classified on the basis of nucleotide sequence diversity in the VP1-encoding ORF2 gene, which divides the majority of human noroviruses into two genogroups (GI and GII). GII-4 noroviruses are the major aetiological agent of outbreaks of gastroenteritis around the world. During a winter season the diversity among the GII-4 noroviruses has been shown to fluctuate, driving the appearance of new virus variants in the population. We have previously shown that sequence data and in silico modelling experiments suggest there are two surface-exposed sites (site A and site B) in the hypervariable P2 domain. We predict these sites may form a functional variant-specific epitope that evolves under selective pressure from the host immune response and gives rise to antibody escape mutants. Results: In this paper, we describe the construction of recombinant baculoviruses to express VLPs representing one pre-epidemic and one epidemic variant of GII-4 noroviruses, and the production of monoclonal antibodies against them. We use these novel reagents to provide evidence that site A and site B form a conformational, variant-specific, surface-exposed site on the GII-4 norovirus capsid that is involved in antibody binding. Conclusion: As predicted by our earlier study, significant amino acid changes at site A and site B give rise to GII-4 norovirus epidemic variants that are antibody escape mutants.

Nicola C Elviss, David J Allen, Daniel Kelly, Joyce Odeke Akello, Sarah Hau, Andrew J Fox, Mark Hopkins, Jade Derrick, Sarah O'Brien, Miren Iturriza-Gomara (2022)Norovirus attribution study: Detection of norovirus from the commercial food preparation environment in outbreak and non-outbreak premises, In: Journal of applied microbiology133(6)3391pp. 3391-3403

Norovirus remains the most significant virological risk that is transmitted via food and the environment to cause acute gastroenteritis. This study aimed to investigate the hypothesis that the contamination of the commercial food production environment with norovirus will be higher in premises that have recently reported a foodborne norovirus outbreak than those that have not. Sampling of commercial food production environments was carried out across a 16-month period between January 2015 and April 2016 in the South East and the North West of England by local authority environmental health departments as part of routine surveillance visits to premises. A total of 2982 samples, 2038 virological and 944 bacteriological, were collected from 256 premises. Sixteen of these premises, six from South East and ten from North West England, were sampled as part of a public health outbreak investigation. Overall, 2038 swabs were submitted for norovirus testing, with an average of eight swabs per premises (range 4 to 23) and a median of seven. Of the premises sampled, 11.7% (30/256) yielded at least one norovirus-positive sample (environmental, and/or food handler hand swab), and 2.5% of the swabs were positive for norovirus. A peak in the positivity rate was seen in the South East in April 2016. No associations were found between norovirus positivity and bacteriology indicators, or between bacteriology indicators and hygiene ratings. This study demonstrates that food premises and food handlers remain a potential source of norovirus transmission and outbreaks.

David J. Allen, Jim J. Gray, Chris I. Gallimore, Jacqueline Xerry, Miren Iturriza-Gomara (2008)Analysis of Amino Acid Variation in the P2 Domain of the GII-4 Norovirus VP1 Protein Reveals Putative Variant-Specific Epitopes, In: PloS one3(1)1485pp. e1485-e1485 Public Library Science

Background. Human noroviruses are a highly diverse group of viruses classified into three of the five currently recognised Norovirus genogroups, and contain numerous genotypes or genetic clusters. Noroviruses are the major aetiological agent of endemic gastroenteritis in all age groups, as well as the cause of periodic epidemic gastroenteritis. The noroviruses most commonly associated with outbreaks of gastroenteritis are genogroup II genotype 4 (GII-4) strains. The relationship between genotypes of noroviruses with their phenotypes and antigenic profile remains poorly understood through an inability to culture these viruses and the lack of a suitable animal model. Methodology/ Principal Findings. Here we describe a study of the diversity of amino acid sequences of the highly variable P2 region in the major capsid protein, VP1, of the GII-4 human noroviruses strains using sequence analysis and homology modelling techniques. Conclusions/Significance. Our data identifies two sites in this region, which show significant amino acid substitutions associated with the appearance of variant strains responsible for epidemics with major public health impact. Homology modelling studies revealed the exposed nature of these sites on the capsid surface, providing supportive structural data that these two sites are likely to be associated with putative variant-specific epitopes. Furthermore, the patterns in the evolution of these viruses at these sites suggests that noroviruses follow a neutral network pattern of evolution.

S. Morter, G. Bennet, J. Fish, J. Richards, D. J. Allen, S. Nawaz, M. Iturriza-Gomara, S. Brolly, J. Gray (2011)Norovirus in the hospital setting: virus introduction and spread within the hospital environment, In: The Journal of hospital infection77(2)106pp. 106-112 Elsevier

Norovirus (NoV) strains were collected over a four-month period during 2009-2010 from hospitalised patients with symptoms of gastroenteritis. These were characterised in order to estimate how many strains were introduced into the hospital from the community. In addition, environmental swabbing was performed after clinical cleaning of bays or wards accommodating infected patients. This was performed in order to assess the efficiency of cleaning and identify any NoV contamination in the environment. A total of eight distinct genetic clusters of NoV GII-4 genotype were identified during the four-month period, with some wards experiencing multiple outbreaks with different GII-4 strains during the season. NoV was detected from 31.4% of environmental swabs post cleaning. Notes trolleys, computer keyboards, soap and alcohol dispensers, blood pressure equipment, pulse oximeters and tympanic thermometers were identified as NoV reservoirs but contamination was also found on surfaces around the bedside environment, and furniture, fixtures and fittings associated with toilets and shower rooms. The combination of detailed virus characterisation and environmental swabbing is a powerful tool for infection control audits to determine the size and scope of an outbreak and to monitor the efficiency of clinical cleaning. (C) 2010 The Hospital Infection Society. Published by Elsevier Ltd. All rights reserved.

Daniel Kelly, David J. Allen, Joyce O. Akello, Sarah Hau, Miren Iturriza-Gómara (2022)A Comparison of Two Methods for Detection of Norovirus RNA in Environmental Swab Samples, In: Applied Microbiology (Basel)2(3)460pp. 460-469

Standardised molecular methods are available for the detection of norovirus from water and specific food items. Detection of norovirus from stool samples also relies on molecular methods, but differences exist between nucleic acid extraction, reverse transcription, and amplification strategies recommended by the ISO 15216-1:2017, and those employed in clinical laboratories. Here, we conduct a direct comparison of two methods for the detection and quantitation of norovirus from a stool sample and from artificially contaminated swabs. We also compare use of linear dsDNA standards as recommended in ISO 15216:2017 against an in vitro-transcribed single-stranded RNA (ssRNA) for estimation of norovirus genome copy number. Our results show that the two methods have comparable sensitivity for the detection of norovirus RNA from a clinical sample or swab. The use of a ssRNA standard revealed that quantitation performed against a linear dsDNA standard consistently underestimated the genome copy numbers by 1.5 to 2 log due to the relative inefficiency of the reverse transcription step. This has important implications for the estimation of the sensitivity of norovirus detection methods, comparability of results across sites, and assessment of viral loads that may be clinically significant or estimated to constitute infectious doses.

Daniel Kelly, Khuzwayo C. Jere, Alistair C. Darby, David J. Allen, Miren Iturriza-Gómara (2021)Complete genome characterization of human noroviruses allows comparison of minor alleles during acute and chronic infections, In: Access microbiology3(3)pp. 000203-000203

Human noroviruses (HuNoVs) circulate globally, affect all age groups and place a substantial burden upon health services. High genetic diversity leading to antigenic variation plays a significant role in HuNoV epidemiology, driving periodic global emergence of epidemic variants. Studies have suggested that immunocompromised individuals may be a reservoir for such epidemic variants, but studies investigating the diversity and emergence of HuNoV variants in immunocompetent individuals are underrepresented. To address this, we sequenced the genomes of HuNoVs present in samples collected longitudinally from one immunocompetent (acute infection) and one immunocompromised (chronic infection) patient. A broadly reactive HuNoV capture-based method was used to concentrate the virus present in these specimens prior to massively parallel sequencing to recover near complete viral genomes. Using a novel bioinformatics pipeline, we demonstrated that persistent minor alleles were present in both acute and chronic infections, and that minor allele frequencies represented a larger proportion of the population during chronic infection. In acute infection, minor alleles were more evenly spread across the genome, although present at much lower frequencies, and therefore difficult to discern from error. By contrast, in the chronic infection, more minor alleles were present in the minor structural protein. No non-synonymous minor alleles were detected in the major structural protein over the short sampling period of the HuNoV chronic infection, suggesting where immune pressure is variable or non-existent, epidemic variants could emerge over longer periods of infection by random chance.

Lisa C Lindesmith, Paul D Brewer-Jensen, Michael L Mallory, Mark R Zweigart, Samantha R May, Daniel Kelly, Rachel Williams, Sylvia Becker-Dreps, Filemón Bucardo, David J Allen, Judith Breuer, Ralph S Baric (2022)Antigenic Site Immunodominance Redirection Following Repeat Variant Exposure, In: Viruses14(6)1293

Human norovirus is a leading cause of acute gastroenteritis, driven by antigenic variants within the GII.4 genotype. Antibody responses to GII.4 vaccination in adults are shaped by immune memory. How children without extensive immune memory will respond to GII.4 vaccination has not been reported. Here, we characterized the GII.4 neutralizing antibody (nAb) landscape following natural infection using a surrogate assay and antigenic site chimera virus-like particles. We demonstrate that the nAb landscape changes with age and virus exposure. Among sites A, C, and G, nAbs from first infections are focused on sites A and C. As immunity develops with age/exposure, site A is supplemented with antibodies that bridge site A to sites C and G. Cross-site nAbs continue to develop into adulthood, accompanied by an increase in nAb to site G. Continued exposure to GII.4 2012 Sydney correlated with a shift to co-dominance of sites A and G. Furthermore, site G nAbs correlated with the broadening of nAb titer across antigenically divergent variants. These data describe fundamental steps in the development of immunity to GII.4 over a lifetime, and illustrate how the antigenicity of one pandemic variant could influence the pandemic potential of another variant through the redirection of immunodominant epitopes.

J. P. Harris, N. L. Adams, B. A. Lopman, D. J. Allen, G. K. Adak (2014)The development of web-based surveillance provides new insights into the burden of norovirus outbreaks in hospitals in England, In: Epidemiology and infection142(8)1590pp. 1590-1598 Cambridge University Press

A new surveillance system for outbreaks of norovirus in English hospitals, the hospital norovirus outbreak reporting system (HNORS), was launched in January 2009. On site investigators were enabled to enter data on outbreaks of norovirus directly onto a tailored system via an internet-based front end. A standard dataset was designed to collect information describing the key epidemiological characteristics of each outbreak. In the period 1992–2008, 1817 suspected and confirmed outbreaks of norovirus in English hospitals were reported to national surveillance. After introduction of the new system there were 3980 reports of outbreaks of suspected and confirmed norovirus received in the years 2009–2011. Data from the new reporting system demonstrates that transmission of norovirus levies a heavy burden on English hospitals. On average, reported outbreaks are associated with 13 000 patients and 3400 staff becoming ill, 8900 days of ward closure and the loss of over 15 500 bed-days annually.

Noelia Carmona-Vicente, Susana Vila-Vicent, David Allen, Roberto Gozalbo-Rovira, Miren Iturriza-Gómara, Javier Buesa, Jesús Rodríguez-Díaz (2016)Characterization of a Novel Conformational GII.4 Norovirus Epitope: Implications for Norovirus-Host Interactions, In: Journal of virology90(17)7703pp. 7703-7714

Human noroviruses (NoVs) are the main etiological agents of acute gastroenteritis worldwide. While NoVs are highly diverse (more than 30 genotypes have been detected in humans), during the last 40 years most outbreaks and epidemics have been caused by GII.4 genotype strains, raising questions about their persistence in the population. Among other potential explanations, immune evasion is considered to be a main driver of their success. In order to study antibody recognition and evasion in detail, we analyzed a conformational epitope recognized by a monoclonal antibody (3C3G3) by phage display, site-directed mutagenesis, and surface plasmon resonance. Our results show that the predicted epitope is composed of 11 amino acids within the P domain: P245, E247, I389, Q390, R397, R435, G443, Y444, P445, N446, and D448. Only two of them, R397 and D448, differ from the homologous variant (GII.4 Den-Haag_2006b) and from a previous variant (GII.4 VA387_1996) that is not recognized by the antibody. A double mutant derived from the VA387_1996 variant containing both changes, Q396R and N447D, is recognized by the 3C3G3 monoclonal antibody, confirming the participation of the two sites in the epitope recognized by the antibody. Furthermore, a single change, Q396R, is able to modify the histo-blood group antigen (HBGA) recognition pattern. These results provide evidence that the epitope recognized by the 3C3G3 antibody is involved in the virus-host interactions, both at the immunological and at the receptor levels. Human noroviruses are the main cause of viral diarrhea worldwide in people of all ages. Noroviruses can infect individuals who had been previously exposed to the same or different norovirus genotypes. Norovirus genotype GII.4 has been reported to be most prevalent during the last 40 years. In the present study, we describe a novel viral epitope identified by a monoclonal antibody and located within the highly diverse P domain of the capsid protein. The evolution of this epitope along with sequential GII.4 variants has allowed noroviruses to evade previously elicited antibodies, thus explaining how the GII.4 genotype can persist over long periods, reinfecting the population. Our results also show that the epitope participates in the recognition of host receptors that have evolved over time, as well.

David J. Allen, Eamonn Trainor, Anna Callaghan, Sarah J. O'Brien, Nigel A. Cunliffe, Miren Iturriza-Gomara (2016)Early Detection of Epidemic GII-4 Norovirus Strains in UK and Malawi: Role of Surveillance of Sporadic Acute Gastroenteritis in Anticipating Global Epidemics, In: PloS one11(4)0146972pp. e0146972-e0146972 Public Library Science

Noroviruses are endemic in the human population, and are recognised as a leading cause of acute gastroenteritis worldwide. Although they are a highly diverse group of viruses, genogroup-II genotype-4 (GII-4) noroviruses are the most frequently identified strains worldwide. The predominance of GII-4 norovirus strains is driven by the periodic emergence of antigenic variants capable of evading herd protection. The global molecular epidemiology of emerging GII-4 strains is largely based on data from outbreak surveillance programmes, but the epidemiology of GII-4 strains among sporadic or community cases is far less well studied. To understand the distribution of GII-4 norovirus strains associated with gastroenteritis in the wider population, we characterised the GII-4 norovirus strains detected during studies of sporadic cases of infectious gastroenteritis collected in the UK and Malawi between 1993 and 2009. Our data shows that GII-4 norovirus strains that have emerged as strains of global epidemic importance have circulated in the community up to 18 years before their recognition as pandemic strains associated with increases in outbreaks. These data may suggest that more comprehensive surveillance programmes that incorporate strains associated with sporadic cases may provide a way for early detection of emerging strains with pandemic potential. This may be of particular relevance as vaccines become available.

Darren J. Wight, Virginie C. Boucherit, Mirella Nader, David J. Allen, Ian A. Taylor, Kate N. Bishop (2012)The Gammaretroviral p12 protein has multiple domains that function during the early stages of replication, In: Retrovirology9(1)83pp. 83-83 Springer Nature

Background: The Moloney murine leukaemia virus (Mo-MLV) gag gene encodes three main structural proteins, matrix, capsid and nucleocapsid and a protein called p12. In addition to its role during the late stages of infection, p12 has an essential, but undefined, function during early post-entry events. As these stages of retroviral infection remain poorly understood, we set out to investigate the function of p12. Results: Examination of the infectivity of Mo-MLV virus-like particles containing a mixture of wild type and mutant p12 revealed that the N- and C-terminal regions of p12 are sequentially acting domains, both required for p12 function, and that the N- terminal activity precedes the C-terminal activity in the viral life cycle. By creating a panel of p12 mutants in other gammaretroviruses, we showed that these domains are conserved in this retroviral genus. We also undertook a detailed mutational analysis of each domain, identifying residues essential for function. These data show that different regions of the N- terminal domain are necessary for infectivity in different gammaretroviruses, in stark contrast to the C-terminal domain where the same region is essential for all viruses. Moreover, chimeras between the p12 proteins of Mo-MLV and gibbon ape leukaemia virus revealed that the C-terminal domains are interchangeable whereas the N- terminal domains are not. Finally, we identified potential functions for each domain. We observed that particles with defects in the N- terminus of p12 were unable to abrogate restriction factors, implying that their cores were impaired. We further showed that defects in the C-terminal domain of p12 could be overcome by introducing a chromatin binding motif into the protein. Conclusions: Based on these data, we propose a model for p12 function where the N- terminus of p12 interacts with, and stabilizes, the viral core, allowing the C-terminus of p12 to tether the preintegration complex to host chromatin during mitosis, facilitating integration.

Catherine M. Smith, David J. Allen, Sameena Nawaz, Zisis Kozlakidis, Eleni Nastouli, Andrew Hayward, Katherine N. Ward (2019)An interactive data visualisation application to investigate nosocomial transmission of infections, In: Wellcome open research4100pp. 100-100 F1000 Research Limited

Background: Healthcare-associated infections represent a major threat to patient, staff and visitor safety. Identification of episodes that are likely to have resulted from nosocomial transmission has important implications for infection control. Routinely collected data on ward admissions and sample dates, combined with pathogen genomic information could provide useful insights. We describe a novel, open-source, application for visualising these data, and demonstrate its utility for investigating nosocomial transmission using a case study of a large outbreak of norovirus infection. Methods: We developed the application using Shiny, a web application framework for R. For the norovirus case study, cases were defined as patients who had a faecal sample collected at the hospital in a winter season that tested positive for norovirus. Patient demographics and ward admission dates were extracted from hospital systems. Detected norovirus strains were genotyped and further characterised through sequencing of the hypervariable P2 domain. The most commonly detected sub-strain was visualised using the interactive application. Results: There were 156 norovirus-positive specimens collected from 107 patients. The most commonly detected sub-strain affected 30 patients in five wards. We used the interactive application to produce three visualisations: a bar chart, a timeline, and a schematic ward plan highlighting plausible transmission links. Visualisations showed credible links between cases on the elderly care ward. Conclusions: Use of the interactive application provided insights into transmission in this large nosocomial outbreak of norovirus, highlighting where infection control practices worked well or could be improved. This is a flexible tool that could be used for investigation of any infection in any hospital by interactively changing parameters. Challenges include integration with hospital systems for extracting data. Prospective use of this application could inform better infection control in real time.

Emmanuel Kofi Quaye, Raymond Lovelace Adjei, Abiola Isawumi, David J Allen, J Gregory Caporaso, Osbourne Quaye (2023)Altered Faecal Microbiota Composition and Structure of Ghanaian Children with Acute Gastroenteritis, In: International journal of molecular sciences24(4)3607

Acute gastroenteritis (AGE) is a disease of global public health importance. Recent studies show that children with AGE have an altered gut microbiota relative to non-AGE controls. Yet, how the gut microbiota differs in Ghanaian children with and without AGE remains unclear. Here, we explore the 16S rRNA gene-based faecal microbiota profiles of Ghanaian children five years of age and younger, comprising 57 AGE cases and 50 healthy controls. We found that AGE cases were associated with lower microbial diversity and altered microbial sequence profiles relative to the controls. The faecal microbiota of AGE cases was enriched for disease-associated bacterial genera, including , and . In contrast, the faecal microbiota of controls was enriched for potentially beneficial genera, including , , , and . Lastly, distinct microbial correlation network characteristics were observed between AGE cases and controls, thereby supporting broad differences in faecal microbiota structure. Altogether, we show that the faecal microbiota of Ghanaian children with AGE differ from controls and are enriched for bacterial genera increasingly associated with diseases.

J P Harris, D J Allen, M. Ituriza-Gomara (2011)Norovirus: changing epidemiology, changing virology. The challenges for infection control, In: Journal of infection prevention12(3)102pp. 102-106 SAGE Publications

Norovirus infection is the commonest cause of outbreaks and sporadic cases of acute gastrointestinal disease in England and Wales. It is estimated that 4.5% of the population are infected by norovirus each year. Some years see more infections than others and occasionally peaks of summer time activity can occur. Current surveillance of norovirus is based on two main sources of information, routine laboratory reporting and reports of norovirus outbreaks. There are still significant barriers impeding a better understanding of the biology and epidemiology of noroviruses. Modern genetic techniques have shed light on ways in which the virus interacts with its host and evades the immune system. Some of these techniques have also led to new tools that may be useful in tracking outbreaks of norovirus, and in turn, to study the effect of potential intervention strategies, aimed at preventing or curtailing transmission within outbreaks.